Radiotherapy has been a widely used therapeutic approach to the treatment of various forms of cancer. However, although radiotherapy certainly has marked an advancement in the treatment of cancer, its imprecision and toxic side effects require that further improvements be made in this therapeutic approach. The major problems presented by radiotherapy are imprecise beam alignment, arising in large part because of equipment limitations, as well as incomplete knowledge of the microscopic distribution of tumor, and radioresistance of poorly oxygenated cells lying in poorly vascularized tumor regions. Imprecise beam alignment, coupled with the difficulty of locating microscopic fingers of tumor growth in order to include these fingers within the treatment region, and the toxic effects of the radiation on the surrounding healthy tissue lead in many instances to therapeutic failure using traditional radiation therapy.
Recent investigations have focused on two approaches to radiation therapy that are intended to overcome some of the limitations of traditional radiotherapy. One such approach involves photon activation therapy (PAT) and the other involves brachytherapy. Applicants have been involved in the development of both of these approaches. The first of these approaches, PAT, is a technique in which the thymidine analog 5'-iodo-2'-deoxyuridine (IdUrd), wherein the iodine is stable .sup.127 I, is administered to a patient with a malignant tumor. As the IdUrd circulates through the body, cells that are dividing and therefore manufacturing DNA incorporate some of the IdUrd into their DNA in place of thymidine. The IdUrd settles primarily in the cells of the tumor because of the rapid cell proliferation in the tumor. The IdUrd itself possesses anticancer activity in that it sensitizes the tumor cells to the lethal effects of photon irradiation.
After the IdUrd has accumulated in the tumor, it is activated with external photons to produce a cytotoxic response in the tissue due to radiation sensitization and the production of high Linear Energy Transfer (LET) radiation in the form of Auger electron distributions (Auger cascades) generated through photoactivation of the stable iodine incorporated in the tumor cell in the IdUrd. The photoactivation can be provided by an external source of x-rays or by an implanted radiation source. PAT has the advantage of combining the anticancer and radiosensitization effects of IdUrd with the high Linear Energy Transfer radiations provided by Auger electrons induced in the iodine. Accumulations of the IdUrd in the tumor permits delivery of high radiation selectively to tumor, with the surrounding normal tissue being traversed by the low energy activating photons and thus suffering little damage. The PAT approach seems to have the most clinical potential in the treatment of tumors of the brain, head and neck.
The second new approach to the use of radiation therapy in the treatment of malignant tumors is brachytherapy, which is radiotherapy in which the source of irradiation is placed close to the surface of the body or within the body cavity. Several radioiosotopic sources are now widely used in the treatment of cancer using brachytherapy; they are .sup.226 Ra, .sup.60 Co, .sup.198 Au, .sup.192 Ir and .sup.125 I. These brachytherapy sources are employed for intracavitary, interstitial and superficial therapy of localized tumors. Of these radioisotopic sources, .sup.125 I is probably the most interesting clinically for several reasons. Iodine's lower energy photons show relatively rapid attenuation, resulting in lower doses to normal tissue outside the treatment area. Also, iodine's lower energy photons permit small amounts of high-Z-material, such as gold or lead foils, to provide almost complete energy absorption and thus gold or lead foil plaques can be used to shield vital body tissue or organs from the photons.
Applicants have now developed a new radioisotopic source, samarium-145 (.sup.145 Sm), which has important applications in both photon activation therapy and brachtherapy.